Description:
BLOOM SYNDROME; BLM
RECQ PROTEIN-LIKE 3; RECQL3
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases
Hereditary Cancers
Chromosome Abnormalities |
| Class |
Repair Defective and Chromosomal Instability Syndromes |
| Class |
Syndromes with Increased Chromosome Breakage |
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Cell Type
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Fibroblast
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Transformant
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Untransformed
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Race
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White
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Ethnicity
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JEWISH/ENGLISH
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Family Member
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1
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Relation to Proband
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proband
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Confirmation
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Clinical summary/Case history
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Species
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Homo sapiens
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Common Name
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Human
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Remarks
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| Passage Frozen |
11 |
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Nucleoside Phosphorylase, Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis and by Chromosome Analysis |
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| CELL CULTURE IDENTIFICATION |
GM04408 and GM03498 are lymphoblast and fibroblast cultures derived from the same patient. Willis et al (Carcinogenesis 10:217-219,1989) showed that both cultures were identical for four different isoenzyme markers (PGM1:1; PEGM3:6a; ESD:1; and PGP:1). In addition, these authors showed that HinfI digested DNA from each of the cell types hybridized with two locus specific hypervariable probes (lambda pg3 and PUM) to give distinct patterns of hybridizing DNA fragments which were identical and unique in comparison with several controls. These data identify these cell cultures as having been derived from the same individual. |
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| DNA LIGASE I AND II |
Willis et al (Carcinogenesis 10:217-219,1989) assayed the DNA ligase I activity in this culture after chromatographic separation of ligases I and II. Their results showed an anomalously low level of DNA ligase I activity which was similar to that observed for other Bloom's syndrome cultures. The DNA ligase I activity was also characterized as having an abnormal heat lability. |
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| SISTER CHROMATID EXCHANGE ANALYSIS |
Willis et al (Carcinogenesis 10:217-219,1989) reported that this fibroblast culture exhibited a high level of spontaneous SCE which was characteristic of Bloom's syndrome cultures. |
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| URACIL DNA GLYCOSYLASE |
Seal et al (Proc Natl Acad Sci USA 85:2339-2343,1988) reported that monoclonal antibody, 40.10.09, to normal uracil DNA glycosylase did not react with the uracil DNA glycosylase from this Bloom syndrome culture. |
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| REPAIR OF UV- OR X RAY-IRRADIATED DNA OR ALKYLATED DNA |
Willis et al (Carcinogenesis 10:217-219,1989) reported that this cell culture showed a hypersensitive response to the cytotoxic effects of ethyl methane sulphonate compared to a control fibroblast culture. |
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| Gene |
RECQL3 |
| Chromosomal Location |
15q26.1 |
| Allelic Variant 1 |
604610.0001; BLOOM SYNDROME |
| Identified Mutation |
6-BP DEL/7-BP INS; In 4 ostensibly unrelated persons of Jewish ancestry, Ellis et al. [Cell 83: 655 (1995)] found homozygosity for a 6-bp deletion/7-bp insertion at nucleotide 2281 of the BLM cDNA. Deletion of ATCTGA and insertion of TAGATTC caused the insertion of the novel codons for LDSR after amino acid 736, and after these codons there was a stop codon. Ellis et al. [Cell 83: 655 (1995)] concluded that a person carrying this deletion/insertion mutation was a founder of the Ashkenazi-Jewish population, and that nearly all Ashkenazi Jews with Bloom syndrome inherited the mutation identical by descent from this common ancestor. |
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| Gene |
RECQL3 |
| Chromosomal Location |
15q26.1 |
| Allelic Variant 2 |
; BLOOM SYNDROME |
| Identified Mutation |
3233delT |
| Remarks |
Clinically affected; B.S. Registry #87; stunted growth; minimal freckling over malar area; normal intelligence; excessive sister chromatid exchange in leukocytes and fibroblasts; 4-fold more sensitive to killing by ethyl methanesulphonate compared to control fibroblast; reduced level of DNA ligase I activity; donor subject is a compound heterozygote: one allele has a 6-bp deletion/7-bp insertion [6-bp del/7-bp ins] at nucleotide 2,281 of the open reading frame of the RECQL3 gene that results in a frameshift and a stop codon and a second allele has 1-bp deletion at nucleotide 3233 [3233delT] of the RECQL3 gene resulting in a frameshift and premature termination; same donor as GM04408 B-lymphocyte. |
| German J, Sanz MM, Ciocci S, Ye TZ, Ellis NA, Syndrome-causing mutations of the BLM gene in persons in the Bloom's Syndrome Registry Human mutation28:743-53 2007 |
| PubMed ID: 17407155 |
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| Foucault F, Vaury C, Barakat A, Thibout D, Planchon P, Jaulin C, Praz F, Amor-Gueret M, Characterization of a new BLM mutation associated with a topoisomerase II alpha defect in a patient with Bloom's syndrome. Hum Mol Genet6:1427-34 1997 |
| PubMed ID: 9285778 |
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| Lu X, Lane DP, Differential induction of transcriptionally active p53 following UV or ionizing radiation: defects in chromosome instability syndromes? Cell75:765-78 1993 |
| PubMed ID: 8242748 |
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| Poot M, Rudiger HW, Hoehn H, Detection of free radical-induced DNA damage with bromodeoxyuridine/Hoechst flow cytometry: implications for Bloom's syndrome. Mutat Res238:203-7 1990 |
| PubMed ID: 1692968 |
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| Nicotera TM, Notaro J, Notaro S, Schumer J, Sandberg AA, Elevated superoxide dismutase in Bloom's syndrome: a genetic condition of oxidative stress. Cancer Res49:5239-43 1989 |
| PubMed ID: 2766291 |
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| Willis AE, Spurr NK, Lindahl T, Concomitant reversion of the characteristic phenotypic properties of a cell line of Bloom's syndrome origin. Carcinogenesis10:217-9 1989 |
| PubMed ID: 2910526 |
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| Seal G, Brech K, Karp SJ, Cool BL, Sirover MA, Immunological lesions in human uracil DNA glycosylase: association with Bloom syndrome. Proc Natl Acad Sci U S A85:2339-43 1988 |
| PubMed ID: 3353381 |
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| Heartlein MW, Tsuji H, Latt SA, 5-Bromodeoxyuridine-dependent increase in sister chromatid exchange formation in Bloom's syndrome is associated with reduction in topoisomerase II activity. Exp Cell Res169:245-54 1987 |
| PubMed ID: 3028845 |
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| Doniger J, Di Paolo JA, Popescu NC, Transformation of Bloom's syndrome fibroblasts by DNA transfection. Science222:1144-6 1983 |
| PubMed ID: 6648529 |
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| Nicotera, Elevated superoxide dismutase activity in Bloom Syndrome fibroblasts. Am J Hum Genet35:49A (1983):1144-6 1983 |
| PubMed ID: 6648529 |
| Passage Frozen |
11 |
| Split Ratio |
1:3 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Percent O2 |
AMBIENT |
| Medium |
Eagle's Minimum Essential Medium with Earle's salts and non-essential amino acids with 2mM L-glutamine or equivalent |
| Serum |
15% fetal bovine serum Not inactivated |
| Substrate |
None specified |
| Subcultivation Method |
trypsin-EDTA |
| Supplement |
- |
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